We have used the carcinogen N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide (FANFT) to induce bladder cancer in rats in order to study the cellular immune response during tumor development. Expression of both natural and antibody-dependent lymphocyte-mediated cytotoxicity was observed to decrease early in tumor development, even though lymphocyte populations appeared unchanged and blastogenesis in mixed lymphocyte/tumor cell culture persisted. In concomitant studies, interferon (IF) stimulated lymphocyte cytotoxicity and prostaglandin E2 (PGE2) inhibited cytotoxicity. Since bladder tumor cells in response to exposure to lymphocytes and macrophages were found to produce significant amounts of PGE2 in vitro, and macrophages have been shown to produce both IF and PGE2, it was felt that the effect of these substances might be important in lymphocyte/macrophage-tumor cell interactions and in the ability of the host to respond to tumor development. The major objectives of this investigation, therefore, are to continue characterization of the cellular immune response during bladder cancer development, to study conditions that determine production of IF and PGE2 during lymphocyte/macrophage-tumor cell interactions, and to assess effects of these substances in the manipulation of the cellular immune response and tumor development in vitro and in vivo. Lymphocyte cytotoxicity would be assessed during tumor development using Chromium 51 release assays. Interactions with macrophages, and the possible role of IF, as determined by viral inhibition assays, and PGE2, as determined by radioimmunoassays, would be studied in vitro, with subsequent application of in vitro interactions in attempts to modulate the cellular immune response and tumor development in vivo. Ultimately, results of in vitro and in vivo studies of the role of cell products (IF, PGE2) in the cellular immune response to tumor development might be applicable clinically in the inhibition of bladder cancer development in man.